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Intragenic deletion in the gene encoding L-gulonolactone oxidase causes vitamin C deficiency in pigs

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Abstract

The absence of L-ascorbic acid (L-AA, or AA) synthesis in scurvy-prone organisms, including humans, other primates, guinea pigs, and flying mammals, was traced to the lack of L-gulonolactone oxidase (GULO) activity. GULO is a microsomal enzyme that catalyzes the terminal step in the biosynthesis of L-AA. Clinical cases of scurvy were described in a family of Danish pigs. This trait is controlled by a single autosomal recessive allele designated od (osteogenic disorder). Here we demonstrate that the absence of GULO activity and the associated vitamin C deficiency in od/od pigs is due to the occurrence of a 4.2-kbp deletion in the GULO gene. This deletion includes 77 bp of exon VIII, 398 bp of intron 7 and 3.7 kbp of intron 8, which leads to a frame shift. The mutant protein is truncated to 356 amino acids, but only the first 236 amino acids are identical to the wild-type GULO protein. In addition, the od allele seems to be less expressed in deficient and heterozygous pigs compared with the normal allele in heterozygous and wild-type animals as determined by ribonuclease protection assay. We also developed a DNA-based test for the diagnosis of the deficient allele. However, we failed to identify the mutated allele in other pig populations.

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Authors and Affiliations

  1. Institute of Animal Sciences, Tannenstrasse 1, ETH-Zentrum, CH-8092 Zurich, Switzerland

    Lara Hasan, Peter Vögeli, Špela Špilar Gerald KramerStranzinger & Stefan Neuenschwander

  2. Swiss Federal Research Station for Animal Production, CH-1725 Posieux, Switzerland

    Peter Stoll

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  1. Lara Hasan
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  2. Peter Vögeli
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  3. Peter Stoll
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  4. Špela Špilar Gerald KramerStranzinger
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  5. Stefan Neuenschwander
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Correspondence to Peter Vögeli.

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Hasan, L., Vögeli, P., Stoll, P. et al. Intragenic deletion in the gene encoding L-gulonolactone oxidase causes vitamin C deficiency in pigs . Mamm Genome 15, 323–333 (2004). https://doi.org/10.1007/s00335-003-2324-6

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  • DOI: https://doi.org/10.1007/s00335-003-2324-6

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